The long-term objectives of the proposed research program are: (i) to quantify, in the conscious resting dog, the contribution of the renal sympathetic noradrenergic nerves to stimulation of renin release under conditions in which renin release is known to be elevated, (ii) to identify the relative roles of renal alpha- and beta-adrenergic receptors in mediating neural stimulation of renin release under these same conditions, and (iii) to determine the physiological role of neurally-mediated increases in plasma renin activity (PRA) in control of arterial blood pressure, vasopressin release, and plasma norepinephrine concentration. All experiments will be performed in conscious, trained dogs with chronically implanted catheters. The effect on PRA of direct renal artery infusion of alpha-and beta-adrenergic blocking agents will be evaluated under each of five different experimental conditions: two for which increased renin release is known or presumed to be due to increased renal nerve activity (dehydration and acutely decreased venous return), one for which the role of the renal sympathetic nerves is disputed (dietary sodium deprivation), and two for which tonic renal nerve activity is postulated to potentiate the renin-secretory response to a non-neural stimulus (decreased renal perfusion pressure and acute diuretic administration). In order to evaluate the physiological significance of increased circulating angiotensin levels during these experimental conditions, mean arterial pressure, plasma vasopressin, and plasma norepinephrine values obtained during protocols in which PRA is elevated (no adrenergic blockade) will be compared with those from protocols in which increased PRA is prevented or reduced by renal adrenergic blockade. Additional experiments will identify the possible physiological mechanisms of alpha-adrenergic stimulation of renin release, and will determine the physiological role of renal presynaptic inhibitory alpha-receptors in control of renin release. The renin-angiotensin system can contribute to the development and maintenance of hypertension. The proposed experiments will increase our understanding of the mode of action of any antihypertensive agent which acts by blocking alpha- or beta- adrenergic receptors, or otherwise interferes with sympathetic nerve activity.